dose escalation study of alx-009 in healthy men and cystic fibrosis (cf) and non-cf bronchiectasis patients

Conditions: Cystic Fibrosis; Bronchiectasis

Summary: this is a phase 1, randomized, double-blind, placebo-controlled study to evaluate the safety, tolerability and pharmacokinetics of a single ascending doses (sad) and multiple ascending doses (mad) of hypothiocyanite (oscn-), bovine lactoferrin (blf) and their combination (alx-009) in healthy male volunteers and patients suffering from cystic fibrosis (cf) and non-cf bronchiectasis (ncfbe).

part i: sad of oscn- and blf in healthy male volunteers (cohorts 1 to 3) - part ii: sad and mad of alx-009 in healthy male volunteers (cohorts 4 and 5) - part iii: mad of oscn- and blf in patients suffering from cystic fibrosis (cohort iii-1) and in healthy volunteers (cohorts iii-2 and iii-3) - part iv: mad of alx-009 in healthy volunteers (part iva - cohorts iv-1a to iv-3a) and in patients (part ivb - cohorts iv-1b to iv-3b)

Eligibility criteria:
inclusion criteria: * healthy male subject or * patient suffering from cystic fibrosis defined as a positive sweat chloride test or cf-causing mutations, documented in the patient's medical record or patient suffering from non-cf and non copd bronchiectasis with a diagnosis confirmed by a chest ct scan demonstrating bronchiectasis in 1 or more lobes documented in the patient's medical record * aged between 18 and 50 years inclusive * subject's body mass index between 18 and 30 kg/m² * subject with normal blood pressure, heart rate, ecg recording and laboratory parameters at the screening visit * subject having given a written informed consent prior to selection * subject covered by health insurance system and/ or in compliance with the recommendations of national law in force relating to biomedical research specific inclusion criteria for patients: * fev1 more than or equal to 60% of predicted normal value * subject in a stable state (no exacerbation for 1 month or prescription of antibiotic by intravenous route) * females of childbearing potential: commitment to consistently and correctly use an acceptable method of birth control for the duration of the trial and for 4 months after the last study drug administration / female of non-childbearing potential: either surgically sterilized or at least 1 year postmenopausal exclusion criteria: * presence of cardiovascular, pulmonary, gastro-intestinal, hepatic, renal, metabolic, haematological, neurologic, psychiatric, systemic or infectious disease * frequent headaches and/or migraines, recurrent nausea and/or vomiting * symptomatic hypotension * blood donation (including in the frame of a clinical trial) within 2 months before administration * general anaesthesia within 3 months before administration * presence or history of drug hypersensitivity, or any allergic disease * medical history of reactions to cow's milk proteins * subject who can not be contacted in case of emergency * history or presence of drug or alcohol abuse * positive hepatitis b surface (hbs) antigen or anti hepatitis c virus (hcv) antibody, or positive results for human immunodeficiency virus (hiv) 1 or 2 tests * subject who, in the judgement of the investigator, is likely to be non-compliant or uncooperative during the study, or unable to cooperate because of a language problem, poor mental development. specific exclusion criteria for study parts iii and iv: * known bronchial hyper-reactivity to drug inhalation * known contra-indication to inhaled salbutamol * subject with bronchial hyper-reactivity, defined by a positive response to bronchodilator with fev1 increase ≥ 200 ml specific exclusion crtieria for patients: * active allergic bronchopulmonary aspergillosis currently treated * medical history of allergic bronchopulmonary aspergillosis in the past 2 years.